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Acute Anxiolytic Effects of Sacubitril/Valsartan in Patients with Heart Failure

Michael Kellner1*,2,3, Alexander Yassouridis4 , Dominik Górski5 , Saddoff Waheed2 , Jan Kähler5 , Klaus Wiedemann1

Objective: Anxiety is a frequent symptom in Heart Failure with Reduced Ejection Fraction (HFrEF). By inhibition of the endopeptidase neprilysin, Sacubitril/Valsartan (S/V) blocks degradation of Atrial Natriuretic Peptide (ANP), which has anxiolytic-like effects in man. In patients suffering from HFrEF we presumed an acute anxiolytic action of S/V and its mediation via ANP.

Methods: 56 patients with decompensated HFrEF were treated with S/V (24 mg/26 mg b.i.d.) or Treatment As Usual (TAU) without S/V in an open, non-randomized observational pragmatic controlled trial. At days 0 and 7, anxiety was assessed using the Hospital Anxiety and Depression Scale (HADS) and plasma levels of ANP and heart failure biomarker N-Terminal pro B-type Natriuretic Peptide (NT-proBNP) were measured.

Results: 35 patients participated on both days. Within one week, HADS-anxiety ratings were significantly decreased under S/V, but not TAU. Plasma ANP and NT-proBNP levels did not influence this finding. A significant treatment group effect on the day 7/day 0-ratios of HADS-anxiety emerged when related to the changes in ANP levels.

Conclusion: First evidence for an acute decrease of anxiety under S/V in patients is provided. This interesting, preliminary finding and the respective role of ANP, but also of other neprilysin substrates, need further study in randomized controlled trials.